化工进展 ›› 2021, Vol. 40 ›› Issue (8): 4463-4472.doi: 10.16085/j.issn.1000-6613.2020-1787

• 生物与医药化工 • 上一篇    下一篇

添加剂对氨基酸多晶型溶液结晶过程影响的研究进展

苏伟怡1(), 刘星1, 郝琪1, 郭攀1, 郝红勋2, 李春利1()   

  1. 1.河北工业大学化工学院,化工节能过程集成与资源利用国家地方联合工程实验室,天津 300130
    2.天津大学 化工学院,天津 300072
  • 收稿日期:2020-09-04 出版日期:2021-08-05 发布日期:2021-01-13
  • 通讯作者: 李春利 E-mail:suweiyi@hebut.edu.cn;lichunli_hebut@126.com
  • 作者简介:苏伟怡(1985—),女,副教授,研究方向为药物多晶型、工业结晶过程调控、分离过程集成等。E-mail:suweiyi@hebut.edu.cn
  • 基金资助:
    河北省自然科学基金(B2020202015);国家自然科学基金(21406049);中国博士后科学基金(2015M581283);河北省重点研发项目(18273609D)

Research progress in the effect of additives on the polymorphic crystallization of amino acids in solution

SU Weiyi1(), LIU Xing1, HAO Qi1, GUO Pan1, HAO Hongxun2, LI Chunli1()   

  1. 1.National-Local Joint Engineering Laboratory for Energy Conservation of Chemical Process Integration and Resources Utilization, School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, China
    2.School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
  • Received:2020-09-04 Online:2021-08-05 Published:2021-01-13
  • Contact: LI Chunli E-mail:suweiyi@hebut.edu.cn;lichunli_hebut@126.com

摘要:

氨基酸的不同晶型往往表现出不同的理化性质和药用效果。因此通过调控氨基酸多晶型溶液结晶过程得到目标晶型非常重要,其中添加剂对不同晶型的影响直接且有效,是控制晶型生产常采用的手段。本文综述了不同种类添加剂对氨基酸多晶型溶液结晶过程的影响。首先,以水溶液中不能直接得到的甘氨酸γ晶型为例,阐明了酸、碱和无机盐对其成核的促进作用,从电荷补偿角度分析了该类添加剂对不同晶型生长过程的影响机理。其次,阐述了tailor-made添加剂对氨基酸晶体形态和晶型的调控作用,重点分析了不同结构的tailor-made添加剂对晶型转变的影响规律。介绍了醇-水等混合溶剂对不同氨基酸多晶型结晶过程的选择性影响。最后,在以上分析的基础上,对通过添加剂分子设计制备不同目标晶型进行了展望。

关键词: 氨基酸, 溶液结晶, 多晶型, 添加剂

Abstract:

Different polymorphs of the amino acid often show different physicochemical properties and medicinal effectiveness. Therefore, it is very important to obtain the target polymorphs by regulating the polymorphic crystallization process of amino acid in solution, in which the influence of additives is direct and effective. Thus, in this paper, the effects of various kinds of additives on the process of polymorphic crystallization of amino acid in solution were reviewed. First of all, taking the γ-glycine as an example which couldn’t be directly obtained from aqueous solution, the promoting effects of acid, alkali and inorganic salt on the nucleation of the crystal were elucidated, and the mechanism for the effectiveness of these additives on the growth of different polymorphs was analyzed on the perspective of charge compensation. Secondly, the influences of tailor-made additives on the crystal morphology and polymorph of amino acids were expounded. Specifically, the influence of tailor-made additives with different structures on polymorphic transformation was analyzed. Then, the selectivity effects of ethanol-water solvent on the polymorphic crystallization of different amino acids were introduced. Finally, based on the above analysis, the preparation of different target crystal forms by molecular design of additives was prospected.

Key words: amino acid, solution crystallization, polymorphs, additives

中图分类号: 

  • O742+.4